Gene_Locus Report

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Gene_locus Report for: human-LIPA

Homo sapiens (Human) lysosomal acid lipase LICH_HUMAN gene LIPA, Lysosomal acid lipase/cholesteryl ester hydrolase (EC:3.1.1.13) LAL cholesterol esterase (wolman disease) Sebelipase

Comment
Responsible for the intracellular hydrolysis of cholesteryl esters and triglycerides that have been internalized via receptor-mediated endocytosis of lipoprotein particles. Important in mediating the effect of LDL (low density lipoprotein) uptake on suppression of hydroxymethylglutaryl-CoA reductase and activation of endogenous cellular cholesteryl ester formation. (from OMIM) Two major disorders, the severe infantile-onset Wolman disease and the milder late-onset cholesteryl ester storage disease (CESD), are seemingly caused by mutations in different parts of the human-LIPA gene. The relatively nonspecific clinical picture of Wolman disease includes poor weight gain, vomiting, diarrhea, increasing hepatosplenomegaly with abdominal protuberance, and death by nutritional failure by 2 to 4 months of age. Sebelipase alfa (Kanuma(R), Kanuma), the first commercially available recombinant human lysosomal acid lipase (LAL), is approved in various countries worldwide, including those of the EU, the USA and Japan, as a long-term enzyme replacement therapy for patients diagnosed with LAL deficiency (LAL-D) P38571 LIPA_HUMAN previously. Gene name LIPA


Relationship
Family|Acidic_Lipase
Block| X
Position in NCBI Life Tree|Homo sapiens
(Below N is a link to NCBI taxonomic web page and E link to ESTHER at designed phylum.)
> cellular organisms: N E > Eukaryota: N E > Opisthokonta: N E > Metazoa: N E > Eumetazoa: N E > Bilateria: N E > Deuterostomia: N E > Chordata: N E > Craniata: N E > Vertebrata: N E > Gnathostomata: N E > Teleostomi: N E > Euteleostomi: N E > Sarcopterygii: N E > Dipnotetrapodomorpha: N E > Tetrapoda: N E > Amniota: N E > Mammalia: N E > Theria: N E > Eutheria: N E > Boreoeutheria: N E > Euarchontoglires: N E > Primates: N E > Haplorrhini: N E > Simiiformes: N E > Catarrhini: N E > Hominoidea: N E > Hominidae: N E > Homininae: N E > Homo: N E > Homo sapiens: N E


Molecular evidence
Database
61 mutations: Table (e.g. : 112kbdel_human-LIPA, A199CfsX12_human-LIPA, D145E_human-LIPA ... more)
1 structure:
6V7N: Structure of human Lysosomal Acid Lipase
No kinetic

Disease: Wolman disease WD, Cholesterol Ester Storage Disease, CESD -



3 substrates: 4-methylumbelliferyl-oleate, 4-methylumbelliferyl-palmitate, P-PMHC
3 inhibitors: ERX-41, Lalistat-1, Lalistat-2
>3 Genbank links 21 more: AL353751, AL513533, AK125193
>3 UniProt links 6 more: P38571, Q6ZUY8, Q5T073
1 Ncbi-nid : 505052
1 Ncbi-pid : 505053
1 Structure : 6V7N
>3 UniProt links 6 more: Q6ZUY8, Q5T073, Q5T770
>3 Interpro links 6 more: Q6ZUY8, Q5T073, Q5T770
>3 Prodom links 6 more: Q6ZUY8, Q5T073, Q5T770
>3 Pfam links 6 more: Q6ZUY8, Q5T073, Q5T770
>3 PIRSF links 6 more: Q6ZUY8, Q5T073, Q5T770
>3 SUPERFAM links 6 more: Q6ZUY8, Q5T073, Q5T770
1 EntrezGene : 3988
1 SNP : 3988
1 UniGene : 643030
1 HUGO HGNC : 6617
2 OMIM : 278000, 613497
1 Ensembl : ENSG00000107798
Sequence
Graphical view for this peptide sequence: human-LIPA
Colored MSA for Acidic_Lipase (raw)
SRGKLTAVDPETNMNVSEIISYWGFPSEEYLVETEDGYILCLNRIPHGRK
NHSDKGPKPVVFLQHGLLADSSNWVTNLANSSLGFILADAGFDVWMGNSR
GNTWSRKHKTLSVSQDEFWAFSYDEMAKYDLPASINFILNKTGQEQVYYV
GHSQGTTIGFIAFSQIPELAKRIKMFFALGPVASVAFCTSPMAKLGRLPD
HLIKDLFGDKEFLPQSAFLKWLGTHVCTHVILKELCGNLCFLLCGFNERN
LNMSRVDVYTTHSPAGTSVQNMLHWSQAVKFQKFQAFDWGSSAKNYFHYN
QSYPPTYNVKDMLVPTAVWSGGHDWLADVYDVNILLTQITNLVFHESIPE
WEHLDFIWGLDAPWRLYNKIINLMRKYQ
Legend This sequence has been compared to family alignement (MSA)
red => minority aminoacid
blue => majority aminoacid
color intensity => conservation rate
title => sequence position(MSA position)aminoacid rate
Catalytic site
Catalytic site in the MSA

SRGKLTAVDPETNMNVSEIISYWGFPSEEYLVETEDGYILCLNRIPHGRK
NHSDKGPKPVVFLQHGLLADSSNWVTNLANSSLGFILADAGFDVWMGNSR
GNTWSRKHKTLSVSQDEFWAFSYDEMAKYDLPASINFILNKTGQEQVYYV
GHSQGTTIGFIAFSQIPELAKRIKMFFALGPVASVAFCTSPMAKLGRLPD
HLIKDLFGDKEFLPQSAFLKWLGTHVCTHVILKELCGNLCFLLCGFNERN
LNMSRVDVYTTHSPAGTSVQNMLHWSQAVKFQKFQAFDWGSSAKNYFHYN
QSYPPTYNVKDMLVPTAVWSGGHDWLADVYDVNILLTQITNLVFHESIPE
WEHLDFIWGLDAPWRLYNKIINLMRKYQ


References
89 more
    Title: Targeting LIPA independent of its lipase activity is a therapeutic strategy in solid tumors via induction of endoplasmic reticulum stress
    Liu X, Viswanadhapalli S, Kumar S, Lee TK, Moore A, Ma S, Chen L, Hsieh M, Li M and Raj GV <19 more author(s)>
    Ref: Nat Cancer, :, 2022 : PubMed

            

    Title: Lysosomal Acid Lipase Drives Adipocyte Cholesterol Homeostasis and Modulates Lipid Storage in Obesity, Independent of Autophagy
    Gamblin C, Rouault C, Lacombe A, Langa-Vives F, Farabos D, Lamaziere A, Clement K, Gautier EL, Yvan-Charvet L, Dugail I
    Ref: Diabetes, 70:76, 2021 : PubMed

            

    Title: Enzyme replacement therapy and hematopoietic stem cell transplant: a new paradigm of treatment in Wolman disease
    Potter JE, Petts G, Ghosh A, White FJ, Kinsella JL, Hughes S, Roberts J, Hodgkinson A, Brammeier K and Wynn RF <10 more author(s)>
    Ref: Orphanet J Rare Dis, 16:235, 2021 : PubMed

            


Other Papers


Send your questions or comments to :
Mail to: Nicolas Lenfant, Thierry Hotelier, Yves Bourne, Pascale Marchot and Arnaud Chatonnet.
Please cite: Lenfant 2013 Nucleic.Acids.Res. or Marchot Chatonnet 2012 Prot.Pept Lett.
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